Author + information
- Wangxiao Tan,
- Yan Sun,
- Qian Zhou and
- Xiaoying Wang
Nitroglycerin (NTG), the representative drug of organic nitrates, has been widely used in the treatment of cardiovascular diseases, including angina pectoris and congestive heart failure for more than a century. The major action of NTG is to dilate blood vessel, reduce cardiac preload and afterload and reduce the myocardial oxygen consumption. However, development of tolerance due to long term administration of NTG can limit its therapeutic effect. The mechanism of NTG tolerance is incompletely defined. Thus, we analyzed the differential gene expression in NTG tolerance rat aorta to identify genes and investigate the potential mechanism of NTG tolerance.
Wistar rats (280 ± 20 g) were randomly divided into control and NTG tolerance group. NTG tolerance rats were administered with NTG 25 mg/kg once a day for 5 days, while the control group received the same dose of saline. In the 5th day of intervention, thoracic aortas were isolated from rats. The Agilent Rat Gene Expression was used to identify the differentially expressed genes. The fold change >= 2.0 and the P value <= 0.05 was set as the threshold for up- and down-regulated genes. Afterwards, Gene Otology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to determine the biological function and pathways affected by these differentially expressed genes.
We got 3147 differentially expressed genes in total, of which 1891 genes were up-regulated (such as Apoc3, Ace2, and Fasn) and 1256 genes were down-regulated (such as Gna14, Gal, and Ngef). By GO analysis, these differentially expressed genes were classified by molecular function, which were mainly related to NADH dehydrogenase (ubiquinone) activity, cytochrome-c oxidase activity, fatty-acyl-CoA binding and calcium ion binding. From the KEGG analysis, we got 90 pathways altered by the differentially expressed genes, including Focal adhesion, Vascular smooth muscle contraction, Calcium signaling pathway, PPAR signaling pathway, Metabolic pathways and Oxidative phosphorylation.
Due to current study, the mechanism of NTG tolerance is dramatically related to NADH dehydrogenase and cytochrome-c oxidase activity, regulated Focal adhesion and PPAR signaling pathway, which may provide a rational basis for further interpretations of NTG tolerance mechanism.